digitoxin

Foxglove (Digitalis spp) is one of the rare wild plants for which humans found a wide range of uses. It’s most well known as an ornamental plant, but its use in making the heart drugs with a deadly potential (digoxin and digitoxin) comes a close second. For Digitalis, the same cardiac glycosides which strengthen the heart beat and saves a life are the chemicals which can cause death, the epitome of the maxim “the dose makes the poison”.

The Herbarium has a number of specimens of the two Digitalis species most common in the UK, D. purpurea and D. lanata. The photos in the post are all of the Digitalis purpurea from the collection of Charles Bailey. Despite these specimens being over a hundred years old, the flowers still had their scent, though made musty over the years. Though they have both a poisonous and a healing potential, they are very appealing plants.

Manchester Museum Herbarium specimen of Digitalis purpurea

Digitalis has been used in folk medicine for many centuries for many conditions, but most consistently for dropsy (fluid retention in the tissues). In the 18th century, the medical effects of Digitalis were put under the scientific scrutiny of the pioneering William Withering (1741-1799). Withering was a doctor practicing around Birmingham drawn into botany by the influence of his wife, a botanical artist. He joined the great tradition of botanist-physicians, and was even known as “the English Linnaeus” by publishing works including A Botanical Arrangement of All the Vegetables Naturally Growing in Great Britain in 1776, the first complete Linnaean classification of the flora of Great Britain.

Digitalis came to Withering’s attention in 1775 when he was asked to deduce the recipe of on a family treatment of last resort for dropsy, which was kept secret by “an old woman in Shropshire”. Withering discerned that the active ingredient was Digitalis purpurea. Intrigued, Withering trialed giving extract of Digitalis to patients attending his free clinic, but with little success. However, the news that a colleague had treated dropsy with the root of Digitalis spurred him on to continue experimenting with the plant. He obtained the dried leaves and gave this powder to his patients in an early precursor of the modern clinical trial. He meticulously recorded the progression of 163 patients taking the drug and found that the dried leaves were effective at relieving the symptoms of dropsy, adjusting the dose as the trial went on. The results were published in 1785 (including failures) in An Account of the Foxglove. The book was remarkable for showing Withering’s willingness to investigate folk remedies rather than dismiss them, to publish negative results and detail side effects. Withering presumed that Digitalis acted as a diuretic to rid the tissues of fluid, but this was only a consequence of Digitalis correcting the underlying heart condition that caused the edema.

Van Gogh’s Portrait of Dr Gachet. Dr Gachet was Van Gogh’s physician, and is pictured here with Digitalis. There is a theory that Van Gogh was suffering chronic Digitalis poisoning at the time of his death, but this hasn’t been sufficiently proved. Source.

Today, the semi-synthetic heart drugs digoxin and digitoxin are derived from Digitalis lanata(rather than Digitalis purpurea used by Withering). Digoxin is the more widely prescribed of the drugs, being used to treat atrial fibrillation and occasionally heart failure. The safe dose of digoxin is around 8 to 12 micrograms per kg of body weight. Doses much higher than this causes poisoning involving vomiting, delirium, yellow vision and a disturbed heart rhythm, which can kill. However, as digoxin is administered under a doctor’s supervision, accidental overdose of the drug is rare. But chillingly, the availability of the drug and the subtleness of the symptoms makes it a choice drug for an unforgivable but rare crime, the murder of patients by healthcare workers. The person believed to be the most prolific serial killer in American history is the nurse Charles Cullen, who is suspected to have killed several hundred patients using very high doses of digoxin and insulin. This case shows that supplies of all drugs should be carefully monitored to avoid their abuse.

Poisoning by Digitalis itself do occur, mostly accidentally by uncareful foragers mistaking it for borage or comfrey, but I have found a report of a woman attempting to poison her husband by adding Digitalis purpurea leaves to a salad. Luckily for these people, the strangely bitter leaves cause vomiting, riding some of the material from the body and sending the person to see a doctor. Poisoning by digoxin in any form can be treated by digoxin-specific antibody, a protein which can bind to digoxin and block its effects, but only if it is caught early enough to be effective.

Digitalis is undoubtedly an infamous poisonous plant, but one that has saved many more lives than it has taken, deliberately or accidentally.